Resveratrol prevents β-cell dedifferentiation in nonhuman primates given a high-fat/high-sugar diet.
Resveratrol prevents β-cell dedifferentiation in nonhuman primates given a high-fat/high-sugar diet.
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作者：
Fiori JL;Shin YK;Kim W;Krzysik-Walker SM;González-Mariscal I;Carlson OD;Sanghvi M;Moaddel R;Farhang K;Gadkaree SK;Doyle ME;Pearson KJ;Mattison JA;de Cabo R;Egan JM
吃高脂肪和高糖分的西式饮食会导致体重增加和许多健康问题，包括发展为2型糖尿病(T2 DM)。啮齿动物研究表明，补充白藜芦醇可以降低血糖水平，保留朗格汉斯胰岛中的β细胞，并改善胰岛素的作用。虽然啮齿动物模型有助于理解β细胞生物学和T2 DM病理的某些方面，但它们无法再现人类疾病的复杂性以及非人类灵长类动物的复杂性。给恒河猴喂以标准饮食(SD)，或高脂/高糖饮食与安慰剂(HFS)或白藜芦醇(HFS+RESV)联合喂养24个月，并在出现明显的血糖异常之前检查胰腺。与SD相比，HFS和HFS+RESV饮食中都出现了葡萄糖刺激的胰岛素分泌增加和胰岛素抵抗。虽然胰岛大小不受影响，但高脂饮食组β细胞显著减少，含有高血糖素和高血糖素样肽1的α细胞显著增加。HFS+RESV猴的胰岛形态与SD相似。补充白藜芦醇后，β细胞转录因子叉头盒O1(FOX01)、NKX6-1、NKX2-2和PDX1表达降低。在白藜芦醇通过Sirtuin 1介导作用的人类胰岛中也观察到了类似的变化。这些发现对治疗患有胰岛素抵抗、糖尿病前期和糖尿病的人类有一定的意义。
Eating a “Westernized” diet high in fat and sugar leads to weight gain and numerous health problems, including the development of type 2 diabetes mellitus (T2DM). Rodent studies have shown that resveratrol supplementation reduces blood glucose levels, preserves β-cells in islets of Langerhans, and improves insulin action. Although rodent models are helpful for understanding β-cell biology and certain aspects of T2DM pathology, they fail to reproduce the complexity of the human disease as well as that of nonhuman primates. Rhesus monkeys were fed a standard diet (SD), or a high-fat/high-sugar diet in combination with either placebo (HFS) or resveratrol (HFS+Resv) for 24 months, and pancreata were examined before overt dysglycemia occurred. Increased glucose-stimulated insulin secretion and insulin resistance occurred in both HFS and HFS+Resv diets compared with SD. Although islet size was unaffected, there was a significant decrease in β-cells and an increase in α-cells containing glucagon and glucagon-like peptide 1 with HFS diets. Islets from HFS+Resv monkeys were morphologically similar to SD. HFS diets also resulted in decreased expression of essential β-cell transcription factors forkhead box O1 (FOXO1), NKX6–1, NKX2–2, and PDX1, which did not occur with resveratrol supplementation. Similar changes were observed in human islets where the effects of resveratrol were mediated through Sirtuin 1. These findings have implications for the management of humans with insulin resistance, prediabetes, and diabetes.
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影响因子：
158.5
作者：
Knowler, WC;Barrett-Connor, E;Nathan, DM
通讯作者：
Nathan, DM
影响因子：
3.7
作者：
Liu Z;Kim W;Chen Z;Shin YK;Carlson OD;Fiori JL;Xin L;Napora JK;Short R;Odetunde JO;Lao Q;Egan JM
通讯作者：
Egan JM
影响因子：
7.7
作者：
Bonner C;Bacon S;Concannon CG;Rizvi SR;Baquié M;Farrelly AM;Kilbride SM;Dussmann H;Ward MW;Boulanger CM;Wollheim CB;Graf R;Byrne MM;Prehn JH
通讯作者：
Prehn JH
DOI：
10.1111/j.1752-8062.2011.00298.x
发表时间：
2011-08
期刊：
Clinical and translational science
影响因子：
--
作者：
Bremer AA;Stanhope KL;Graham JL;Cummings BP;Wang W;Saville BR;Havel PJ
通讯作者：
Havel PJ
影响因子：
64.8
作者：
Baur, Joseph A.;Pearson, Kevin J.;Sinclair, David A.
通讯作者：
Sinclair, David A.